Calcitonin, calcitonin Gene-related peptide (CGRP) and islet amyloid polypeptide (IAPP) have similarities in their structure. Calcitonin is a polypeptide hormone with 32 amino acid residues. By binding to the calcium ion, it can modulate the concentration of calcium ion in blood (Breimer, et al., 1988, Biochem. J. 255:377-390). CGRP is a polypeptide hormone with 39 amino acid residues. It can cause vasodilatation in different vessels (including coronary artery, blood vessel of brain, and the entire vascular system). IAPP is a polypeptide hormone with 37 amino acid residues. It can selectively inhibit glucose metabolism and glycogen synthesis which are induced by insulin (Nishi et al., 1990, J. Biol. Chem. 265: 4173-4176).
In almost all organisms, the three proteins share a conserved structural motif: C-[SAGDN]-[STN]-x (0,1)-[SA]-T-C-[VMA]-x (3)-[LYF]-x (3)-[LYF], and the two cysteines was bonded by a disulfide bond.
The conserved structural motif found in those three proteins is shown below: where * denotes conserved amino acid residues, C denotes the conserved cysteine. There are two conserved cysteines in the N-terminal, and the C-terminal of the protein was amidated. This conserved motif apparently plays a critical role to the physiological functions of calcitonin, CGRP and IAPP.
It is known that calcitonin is essential in the modulation of calcium concentration in the blood. It is used to treat infant hyperglycemia of unknown causes, and adult hypercalcimia caused by hyperparathyroidism. Calcitonin is also important in preventing loss of bone mass and decrease in bone density. Calcitonin deficiency will cause osteoporosis (BMJ, 1989; 298: 1215-6; Biochem J Oct. 15, 1988; 255: 377-90).
Research on the effect of CGRP on the brain and other tissues showed that CGRP can cause vasodilaiton, and it is an important regulator of blood flow and blood vessel tension. Furthermore, CGRP is important in the control of certain nervous system functions, actions of human cell and regulation of the endocrine system.
As discussed above, calcitonin plays an important role the regulation of many biological processes, which regulation is believed to require numerous proteins. It is, therefore, very important to identify additional proteins involved in the regulatory process. The isolation of the calcitonin 11 gene of the present invention enables the identification of its function under healthy and diseased conditions.